Enzymatic defect

Name Alternative Designation Enzymatic Defect Urinary Metabolites... 

In addition to the specimens discussed above, it is common for the laboratory of Neonatology to process the erythrocytes and the leukocytes for enzymatic defects of genetic origin including aberrant hemoglobin identification. The laboratory which services the adult would be called upon to do these tests much less commonly. 

The well-known fact that in irreversibly damaged cells, respiratory control is lost and is accompanied by oxidation of cytochromes a and as, as well as NADH (Taegtmeyer et al., 1985), was originally thoug it to be due to substrate deficiency (Chance and Williams, 1955) but may be due to an enzymatic defect resulting in an inability to metabolize NADH-linked substrates (Pelican etal., 1987). It seems likely therefore that return of function is dependent on preservation of mitochondrial membrane integrity, and the structure and activities of respiratory chain (R.C) complexes I-IV (Chance and Williams, 1955). 

Diagnosis of a urea cycle defect in the older child can be elusive. Patients may present with psychomotor retardation, growth failure, vomiting, behavioral abnormalities, perceptual difficulties, recurrent cerebellar ataxia and headache. It is therefore essential to monitor the blood ammonia in any patient with unexplained neurological symptoms, but hyperammonemia is inconstant with partial enzymatic defects. Measurement of blood amino acids and urinary orotic acid is indicated. 

C18. Cross, R. T., Hurwitz, R. E., and Marks, P. A., An hereditary enzymatic defect in erythrocyte metabolism Glucose-6-phosphate dehydrogenase deficiency. J. Clin. Invest. 37, 1170-1184 (1958). 

Connective tissue is composed of apparently very different cells metabolically it is dynamic undergoing continual turnover and so to maintain health means that a balance must be achieved between biosynthesis and degradation. Cells in connective tissue are usually found embedded within a matrix composed of proteins with variable amounts of proteoglycan and genetically determined enzymatic defects in the production of the matrix may result in often serious pathologies. Metabolism in... 

Congenital enzymatic defects in the adrenal biosynthetic pathways lead to diminished cortisol and aldosterone production and release. In these conditions, corticotrophin secretion is increased, and adrenal hyperplasia occurs, accompanied by enhanced secretion of steroid intermediates, especially adrenal androgens. More than 90% of cases of congenital adrenal hyperplasia are due to 21-hydroxylase deficiency, which is cre-afed by mufafions in fhe CYP21 gene encoding fhe en-... 

Wolf B, Grier RE, Allen RJ, Goodman SI, Kien CL (1983) Biotinidase deficiency the enzymatic defect in late-onset multiple carboxylase deficiency. Clin Chim Acta 131 273-281... 

Mudd SH, Finkelstein JD, Irreverre F Laster L. Homocytinuria an enzymatic defect. Science 1964 143 1443-1445. 

Individuals who are deficient in HMG-CoA lyase are unable to complete the metabolism of leucine. The increased urinary excretion of 3-hydroxy-3-methylglutaric acids is the primary biochemical criterion that distinguishes this particular enzymatic defect from other defects in enzymes of leucine catabolism that also result in metabolic acidosis and abnormal organic aciduria. There is also substantial urinary excretion of intermediates of leucine catabolism, such as 3-methylglutaconic acid, and their metabolites, including 3-hydroxy-isovaleric acid produced from isovaleric acid. 

Deybach JC, de Vemeuil H, Nordmann Y (1981) The inherited enzymatic defect in prophyria variegata. Hum Genet 58 425 128... 

Plaitakis A, Nicklas WJ, Desnick RJ (1979) Glutamate dehydrogenase deficiency in three patients with spinocerebellar ataxia a new enzymatic defect Trans Am Neurol Assoc 104 54-57 Plaitakis A, Nicklas WJ, Desnick RJ (1980) Glutamate dehydrogenase deficiency in three patients with spinocerebellar syndrome. Ann Neurol 7 297-303... 

Lipid Storage Diseases Enzymatic Defects and Clinical Implications, ... 

Ultraviolet light produces pyrimidine dimers in human DNA, as it does in E. coli DNA. Furthermore, the repair mechanisms are similar. Studies of skin fibroblasts from patients with xeroderma pigmentosum have revealed a biochemical defect in one form of this disease. In normal fibro-blasts, half the pyrimidine dimers produced by ultraviolet radiation are excised in less than 24 hours. In contrast, almost no dimers are excised in this time interval in fibroblasts derived from patients with xeroderma pigmentosum. The results of these studies show that xeroderma pigmentosum can be produced by a defect in the excinuclease that hydrolyzes the DNA backbone near a pyrimidine dimer. The drastic clinical consequences of this enzymatic defect emphasize the critical importance of DNA-repair processes. The disease can also be caused by mutations in eight other genes for DNA repair, which attests to the complexity of repair processes. 

Sodium benzoate Sodium benzoate has already been successfully used to treat congenital enzymatic defects of the urea synthesis (M. L. Batshaw et at, 1981). In HE, the administration of sodium benzoate or sodium phenylacetate (each 10 g/day) achieved clinical success equivalent to lactulose therapy in ca. 80% of cases. (122, 144, 159) These substances (which are cheap and practically free of side effects) lead to an increased excretion of nitrogen through the conjugation of glycine and glutamine, whereby ammonium is bound as hippuric acid and excreted renally (bypassing the urea cycle). 

Mucolipidoses are characterized by a combined metabolic disorder of mucopolysaccharides, lipids, and glycoproteins. Lysosomal storage and foamy swollen Kupffer cells with hepatomegaly may be seen. In some of the numerous types, the underlying enzymatic defects have not yet been detected. Type II is also called Leroy syndrome (J.G. Leroy et al., 1967). Due to distinctive cytoplasmic inclusions in fibroblast cultures, this disorder is also known as inclusion cell disease (J.G. Leroy et al., 1971). Foamy altered stellate cells, macrophages and also epithelioid foam cell granulomas are found. 

This is a very rare form of chronic hepatic porphyria. As with PCT, the enzymatic defect is a deficiency of uroporphyrinogen decarboxylase. However, the genetic defect is homozygous. It may also be caused by exogenous factors. HEP manifests in early childhood with high photosensitivity, sclerodermia, hypertrichosis and anaemia. The liver shows red fluorescence. Histologically, siderosis and non-specific hepatitis are found. Development of cirrhosis is possible. No effective therapy is known. (314, 316)... 

However, the precise localization of the enzymatic defect in bile acid synthesis in CTX (microsomal 24S hydroxylation or mitochondrial 26-hydroxylation) awaits the determination of which side chain oxidative mechanism is quantitatively most important in bile acid synthesis. Until then, both mechanisms must be considered (56,64,65). 

Deficiencies of any of these red cell enzymes may result in impaired ATP generation and consequently loss of function of the erythrocyte. By far the majority of these disorders are hereditary in nature, although acquired deficiencies have been described, mainly in malignant disorders involving the bone marrow. Hereditary enzymatic defects in these pathways disturb the erythrocyte s integrity, shorten its cellular survival, and produce chronic nonspherocytic hemolytic anemia (CNSHA). Deficiencies of some enzymes, however, do not lead to chronic hemolytic anemia, but to acute episodes of severe hemolysis when there is increased oxidative stress on the red cell (as in some types of glucose-6-phosphate dehydrogenase deficiency). 

Deybach JC, Da Silva V, Nordman Y. The inherited enzymatic defect in porphyria variegate. Hum Genet 1981 58 425-8. 

Bacteriological and enzymatical defects due to insufficient pasteurisation and unhygienic processing procedures. Results are insufficient shelf-life (fermentation and mould formation) or enzymatical clarification of naturally cloudy juices (instability). 

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